Septic acute kidney injury (AKI) occurs between 15% and 20% of all intensive care unit admissions and its mortality ranges from 20% to 60%. The incidence and mortality of septic AKI has remained high throughout the last 10 years, whereas our understanding of septic AKI pathogenesis has remained limited. Current evidence about the pathophysiology of septic AKI will be reviewed and areas that require further investigation will be discussed. Improvement of knowledge about this condition seems to be most important in order to find valid diagnostic exams to exactly identify septic AKI and effective therapies to treat it: both of them are currently lacking. Finally, new preventive strategies might be experimented in order to protect critically ill patients from septic AKI.